Negative Serology by Immunoenzymatic Test (EIA) in HIV-infected Children Treated Early With Antiretroviral in the ANRS-Pediacam Study: Pathophysiological Mechanisms

HIV Infections Clinical Trial

— PediacamNEG  

Official title:

Negative Serology by Immunoenzymatic Test (EIA) in HIV-infected Children Treated Early With Antiretroviral in the ANRS-Pediacam Study: Pathophysiological Mechanisms

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06302933
• Other study ID #: ANRS 12414 PediacamNEG
• Status: Recruiting
• Phase: N/A
• Start date: May 2, 2024
• Est. completion date: August 30, 2025

Study information

• Verified date: June 2024
• Source: ANRS, Emerging Infectious Diseases
• Contact: Mathurin C Tejiokem, Doctor
• Phone: +237222231803
• Email: tejiokem[@]pasteur-yaounde.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of the study is to identify the pathophysiological mechanisms responsible for the induction and maintenance of negative serologies by EIA tests in HIV-infected children treated early with HAART in the ANRS 12225-Pediacam III cohort in Cameroon

The hypothesis of better control of HIV infection through interactions between immunological, viral, and genetic factors was made to build the following objectives:

• Immunological aspect: lack of humoral response or immune activation

• Virological aspect: Reduced HIV reservoir size

• Determine the HLA phenotype in the different groups of children included and the KIR genotypes.

Description:

There will be two phases of the study :

• A retrospective phase: case-control study The analyzed data are those collected previously or measured from the already available bio bank, within the framework of the Pediacam III cohort during the primary infection phase before the initiation of HAART, at 6 months after the end of the first series of EPI vaccines, and at 2 years.

• A prospective phase: cross-sectional study Based on an ad hoc bio bank created for parameters we couldn't measure on the existing bio bank

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 451
• Est. completion date: August 30, 2025
• Est. primary completion date: August 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

Case control study

• Children included and followed in the ANRS 12225 study - Pediacam III

• Having plasma samples in the bio bank during the above-mentioned periods Case:children with at least one negative HIV serology made by ELISA, permanent or transientduring follow-up.

Control (4 groups)

• HIV-infected children with positive serology and viral load (VL) <400 copies /ml

• HIV-infected children with positive serology and VL =400 copies / ml

• HIV-uninfected children born to HIV-positive mothers

• HIV-uninfected children born to HIV-uninfected mothers Selection of cases and controls will be matched on gestational age (premature <37, term =37 weeks) and year of birth (2007-2008 and 2009-2010).

Cross sectional study Inclusion criteria

• All children still followed in the ANRS - Pediacam III cohort

• Written consent of one of the parents or the guardian and assent of the child if aged = 11 years and complete disclosure of HIV statusfor infected children for participation to the study.

Exclusion Criteria:

• Refusal by one of the parents or the guardian for the child's participation in the study

• No assent of the child (if aged = 11 years and with complete disclosure of HIV status, for infected children)

Related Conditions & MeSH terms

• HIV Infections

Intervention

Biological:
• Blood sampling
Blood samples collected from children followed in the Pediacam III ANRS12225 cohort

Locations

Country	Name	City	State
Cameroon	Hôpital de Jour - Hôpital Laquintinie de Douala	Douala
Cameroon	Unité Pédiatrique de Jour - Centre Mère et Enfant de la Fondation Chantal Biya	Yaounde
Cameroon	Service de Pédiatrie - Centre Hospitalier d'Essos	Yaoundé

Sponsors (9)

Lead Sponsor	Collaborator
ANRS, Emerging Infectious Diseases	Centre Hospitalier D'essos, Centre Hospitalier Universitaire d'Orléans, Centre Mère et Enfant de la Fondation Chantal Biya, Centre Pasteur du Cameroun, Hopital Universitaire Robert-Debre, Hospital General De Douala, Institut Pasteur, Université Paris-Sud

Country where clinical trial is conducted

Cameroon, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Level of pro-inflammatory and anti-inflammatory cytokines, chimiokines in the plasma	Measure of sCD14 (µg/ml). Levels of these biomarkers will be compared across all groups.	18 months
Primary	Level of pro-inflammatory and anti-inflammatory cytokines, chimiokines in the plasma	Measure of BAFF using luminex or commercially available ELISA quantification kits. Levels of these biomarkers will be compared across all groups.	18 months
Primary	Level of pro-inflammatory and anti-inflammatory cytokines, chimiokines in the plasma	Measure of CXCL13 using luminex or commercially available ELISA quantification kits. Levels of these biomarkers will be compared across all groups.	18 months
Primary	Level of pro-inflammatory and anti-inflammatory cytokines, chimiokines in the plasma	Measure of TNF-a (pg/ml). Levels of these biomarkers will be compared across all groups.	18 months
Primary	Level of pro-inflammatory and anti-inflammatory cytokines, chimiokines in the plasma	Measure of IL-10 (pg/ml). Levels of these biomarkers will be compared across all groups.	18 months
Primary	Level of pro-inflammatory and anti-inflammatory cytokines, chimiokines in the plasma	Measure of IP-10 (pg/ml). Levels of these biomarkers will be compared across all groups.	18 months
Primary	Level of pro-inflammatory and anti-inflammatory cytokines, chimiokines in the plasma	Measure of TRAIL (ng/ml). Levels of these biomarkers will be compared across all groups	18 months
Secondary	- Humoral response to vaccines against tetanus, pertussis, and viral hepatitis B	Serum concentrations of human IgG antibodies against tetanus-toxoid, pertussis, and viral hepatitis B will be measured using commercially available ELISA quantification kits and results will be given as IU/mL	18 months
Secondary	- Functional and phenotypic characterization of B and T lymphocytes	Level (cells/µL or percentage) of T and B-cell lymphocytes subpopulations will be assess in blood using flow cytometry. Functional characterization of T and B lymphocytes will be done by cell culture following by cytokine production titration	18 months
Secondary	- Size of the HIV reservoir	Measure total (copies/million PBMC), integrated (copies/million PBMC), unintegrated (copies/million PBMC) HIV DNA level in Peripheral Blood Mononuclear Cells (PBMC)	18 months
Secondary	- Residual viremia in perinatally HIV-infected adolescent	Any detectable HIV-RNA below 50 copies/mL	18 months
Secondary	- Level of HIV plasma p24	Measure plasma level of HIV p24 antigen (fg/ml) using ultrasentsitive technique called Simoa (Single molecule array)	18 months
Secondary	- HLA phenotype and the KIR genotypes	HLA-B (27 et 57), HLA-B35 ou 53, HLA-C16:01+KIR2DL3+	18 months